The typical process for maintaining a homeostatic balance (ie a negative feedback loop) has three main components which act depending on the stimulus received. A sensor, also referred to a receptor, is the component of a feedback system that monitors a physiological value. This value or status is conveyed to the control centre. The control centre is the component in a feedback system that compares the value to the normal range. If the value deviates too much from the set point, then the control centre activates an effector. An effector is the component in a feedback system that causes a change to reverse the situation and return the value to the normal range (Figure 6.1).

In order to set the system in motion, a stimulus must drive a physiological parameter beyond its normal range (that is, beyond homeostasis). This stimulus is “heard” by a specific sensor.

Maintaining homeostasis requires that the body continuously monitor its internal conditions. From body temperature to blood pressure to levels of certain nutrients, each physiological condition has a particular set point. A set point is the physiological value around which the normal range fluctuates. A normal range is the restricted set of values that is optimally healthful and stable, such as human body temperature, where the set point is approximately 37°C (98.6°F) (Figure 6.1b). Physiological parameters, such as body temperature and blood pressure, tend to fluctuate slightly around this set point and feedback systems allow to maintain this within a normal range. Control centres in the brain and other parts of the body monitor and react to deviations from the homeostasis set point using negative feedback. Negative feedback is a mechanism that reverses a deviation from the set point. Therefore, negative feedback maintains body parameters within their normal range. The maintenance of homeostasis by negative feedback goes on throughout the body at all times, and an understanding of negative feedback is thus fundamental to an understanding of human physiology.

Glucose Regulation in Humans

Blood glucose concentrations in the body vary constantly – they can increase due to eating and stress and decrease if you exercise more than usual, for example. For the control of blood glucose, specific endocrine cells in the pancreas detect excess glucose (the stimulus) in the bloodstream. These pancreatic beta cells respond to the increased level of blood glucose by releasing more of the hormone insulin into the bloodstream. The insulin signals skeletal muscle fibres, fat cells (adipocytes) and liver cells by binding to the insulin receptors on these cells. When this binding occurs, special transport systems open up in the cell membrane and glucose moves into the cell via these transport systems. This removes the excess glucose from the bloodstream. As glucose concentration in the bloodstream drops, the decrease in concentration—the actual negative feedback—is detected by pancreatic cells and insulin release decreases to basal levels. This prevents blood glucose concentrations from continuing to drop below the normal range. If this does occur, another hormone (glucagon) is released from pancreatic alpha cells that signal the increased insulin signalling to return to normal and signals other cells to release glucose into the bloodstream – maintaining the blood glucose within the normal levels for the body. This constant monitoring ensures glucose remains in the normal range (Figure 6.2).

Sometimes however, this regulation does not work as expected. The hallmark of Type 1 diabetes is very high blood glucose which is unable to be regulated normally through negative feedback loops as the body cannot produce or cannot produce enough of one crucial hormone – insulin. In Type 1 diabetes, the insulin has to be added to the body in the form of injections generally but research into alternatives includes pancreatic beta cell transplants for example.

Body Temperature Regulation in Humans

Humans have a similar temperature regulation feedback system that works by promoting either heat loss or heat gain (Figure 6.1b). When the brain’s temperature regulation centre receives data from the sensors indicating that the body’s temperature exceeds its normal range, it stimulates a cluster of brain cells referred to as the “heat-loss centre.” This stimulation has three major effects:

1. Blood vessels in the skin begin to dilate allowing more blood from the body core to flow to the surface of the skin allowing the heat to radiate into the environment.
2. As blood flow to the skin increases, sweat glands are activated to increase their output. As the sweat evaporates from the skin surface into the surrounding air, it takes heat with it (ie evaporative cooling).
3. The depth of respiration increases and a person may breathe through an open mouth instead of through the nasal passageways. This further increases heat loss from the lungs.

In contrast, activation of the brain’s heat-gain centre by exposure to cold reduces blood flow to the skin and blood returning from the limbs is diverted into a network of deep veins. This arrangement traps heat closer to the body core and restricts heat loss. If heat loss is severe, the brain triggers an increase in random signals to skeletal muscles, causing them to contract and producing shivering. The muscle contractions of shivering release heat while using up ATP. The brain triggers the thyroid gland in the endocrine system to release thyroid hormone, which increases metabolic activity and heat production in cells throughout the body. The brain also signals the adrenal glands to release adrenaline (epinephrine), a hormone that causes the breakdown of glycogen into glucose, which can then be used as an energy source. The breakdown of glycogen into glucose also results in increased metabolism and heat production.

In newborns (humans and other placental mammals) however, this shivering mechanism doesn’t work, so to maintain body temperature, babies have more brown adipose (fat) tissue than is found in adults (Figure 6.3). This special type of adipose tissue will convert stored energy to heat (non-shivering thermogenesis) allowing core body temperature to be maintained and as infants increase muscle mass, improve nervous innervation and become more active, the brown adipose tissue depots decrease in size over time.